AB0018 IMPACT OF AN EX-NOVO INDUCED ADAPTIVE IMMUNE RESPONSE ON CXCL13 SERUM LEVELS IN ESTABLISHED AUTOANTIBODY-POSITIVE RHEUMATOID ARTHRITIS
Authors: E. Bozzalla Cassione, M. Mansoubi, T. Luvaro, I. Mazzucchelli, B. Xoxi, L. De Stefano, S. Bugatti, C. Montecucco, A. Manzo
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> C-X-C motif chemokine ligand 13 (CXCL13) is a chemokine involved in the recruitment of B cells in secondary lymphoid organs and ectopic inflamed sites. Recent studies in animals models and in healthy individuals have shown that serum levels of CXCL13 correlate with GC activity after immunization, pointing at their role as an early biomarker of the adaptive immune response. In rheumatoid arthritis (RA) CXCL13 systemic expression has been shown to be upregulated. However, the factors involved in CXCL13 systemic upregulation and its significance as putative biomarker in patients with autoimmune diseases are currently unclear. <h3>Objectives</h3> To analyze the dynamics of CXCL13 systemic expression over time in RA after controlled induction of an adaptive immune response. <h3>Methods</h3> Fifty-five autoantibody-positive RA patients with established disease under stable treatment with b/tsDMARDs and with no evidence of previous SARS-CoV-2 infection were included in the study. All patients received two doses of the BNT162b2 vaccine at a three weeks interval. Serum samples were collected at the time of the first BNT162b2 dose (baseline - BL), after three weeks at the time of the second dose (post dose 1 – PD1) and after two further weeks (post dose 2 – PD2). At each time point CXCL13 (pg/mL) and SARS-CoV-2 anti-spike protein antibody titres were measured. <h3>Results</h3> The majority of patients were female (n=42, 76%) and both ACPA and RF positive (n=42, 76%). All patients were receiving stable b/tsDMARD treatment (anti-CTLA4: 23 patients [41.8%], JAKi: 16 [29%], anti-IL6: 8 [14.5%] and anti-TNF alpha: 8 [14.5%]). At baseline the median (IQR) CXCL13 values were 81.1 (58.6-125) and all patients were negative for SARS-CoV-2 anti-spike protein antibody. Effective immunization was confirmed in all patients, in particular in 22/55 (40%) after the first dose and in 55/55 (100%) after the second dose, with a significant increase in SARS-CoV-2 anti-spike protein IgG antibody titer at PD2 (median [IQR], 142 [95.4-224]). Despite the effective induction of an adaptive immune response, no significant changes in the median (IQR) values of CXCL13 were observed at PD1 (three weeks after induction: 92.2 [61.8-141]) and PD2 (two weeks after booster: 74.2 [56-126]) with respect to each other and compared to baseline (Friedman p-value=0,947). Sub-analyses based on patients’ stratification according to the b/tsDMARD treatment, confirmed a non-significant variation in CXCL13 titers between baseline, PD1 and PD2 in all groups (Friedman p-value= 0,911). Further sub-analyses limited to patients with baseline-PD1 value of CXCL13&lt;100 pg/ml (to exclude potential biases derived from high starting value of CXCL13 titers on the delta of response) confirmed the absence of significant changes (Friedman p-value= 0.237). <h3>Conclusion</h3> At the time-point analysed, the induction of an adaptive immune response <i>per se</i> does not appear sufficient to impact on of the expression dynamics of serum CXCL13 in established autoantibody-positive RA. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.